The Molecular Imaging Branch (MIB) mainly aims to exploit positron emission tomography (PET) as a radiotracer imaging technique for investigating neuropsychiatric disorders, such as depression, schizophrenia and Alzheimer's disease. Fundamental to the mission of the MIB is the development of novel radiotracers that can be used with PET to deliver new and specific information on molecular entities and processes in the living human or animal brain (e.g. regional neuroreceptor concentrations, neurotransmitter synthesis, enzyme concentrations, regional metabolism, amyloid deposition). PET is uniquely powerful for this purpose provided that it can be coupled to appropriate radioactive probes (PET radiotracers). The chemical development of these probes is the key to exploiting the full potential of PET in neuropsychiatric research, but is also recognised as being highly challenging and demanding. The PET Radiopharmaceutical Sciences Section of the MIB opened in 2002 and is now established to fulfill the need for a concerted effort on PET radiotracer discovery (a process that has some parallels with drug discovery). The first phase of laboratories (~ 4000 sq ft) are equiped and functioning with state-of-the-art facilities for medicinal chemistry and automated radiochemistry with positron-emitting carbon-11 (t1/2 = 20 min) and fluorine-18 (t1/2 = 110 min). These short-lived radioisotopes must be produced on a daily basis from the adjacent cyclotrons of the NIH Clinical Center. A scientific program is now well established, focusing on developing novel radiotracers for brain receptors or proteins implicated in neuropsychiatric disorders [e.g. cannabinoid (CB-1), serotonin (5-HT1A), alpha-2, AMPA, CRH, NET, PBR, glutamate (mGluR5)and beta-amyloid protein deposits). Initial progress in some of these areas (e.g. NET, 5-HT1A, CB-1, PBR and glutamate)is already encouraging for eventual successful radioligand development. Thus many candidate radioligands were prepared and then found in PET experiments to give detectable receptor-specific signals in animals in vivo with PET. Methodology underpinning these developments was also advanced in areas such as polymer-supported labeling reactions, microwave-enhanced chemistry and radiochemistry and the development of micro-reactors for radiochemnistry. New analytical methods have also been developed and exploited to understand the biochemical fate of radiotracers - information which is need to fully understand the results from PET experiments and to derive meaningful merasures, such as brain receptor concentrations. Productive collaborations are established with external academic laboratories, and also with Pharma through a series of CRADAs (Cooperative Research and Development Agreements). The laboratory is already producing some radiotracers for regular PET investigations in animals {e.g. [18F]FECNT and [11C]PE2I (for dopamine transporter), [11C]NNC 112 (for dopamine-type-1 receptor), [18F]SPA-RQ (for NK1-receptor), [18F]Fallypride (for dopamine type-2 receptor imaging), [11C]Rolipram (for PDE4 enzyme)}and some of these are now available for brain imagimg in human subjects and clinical research protocols under FDA approved INDs. A second phase of laboratories (2000 sq ft), which will expand the facility for organic synthesis, radiochemistry and biological studies, is now planned.